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The effect of unique molecular identifier family size using tumor-informed circulating tumor-DNA analysis in childhood cancers
J Mol Diagn. 2026 Sep 11:S1525-1578(26)00156-X. doi: 10.1016/j.jmoldx.2026.08.002. Online ahead of print.
ABSTRACT
Analysis of circulating tumor-DNA (ctDNA) provides a molecular assessment that can complement routine imaging in childhood cancer management. Detailed monitoring of ctDNA levels may provide information on treatment efficacy and resistance, minimal residual disease and allows for early detection of relapse. Here, tumor-informed ctDNA analysis was applied to 90 blood plasma samples collected from eight children with malignant tumors. Four to ten tumor-specific mutations per patient were assessed using SiMSen-Seq, a digital sequencing approach utilizing unique molecular identifiers (UMIs). The effects of individual SiMSen-Seq assays and plasma samples were evaluated in relation to their impact on background error rate, number of detected target molecules and mutant calling using different UMI family size cutoff settings. The use of at least two sequencing reads per UMI provided the best overall performance by generating the highest number of detected target molecules and hence the optimal chance to detect low-frequent mutations. Data were consistent between SiMSen-Seq assays and plasma samples, providing robust ctDNA profiling over time for all patients. In conclusion, the results show that optimal use of UMIs in tumor-informed ctDNA analysis enables sensitive molecular readout that can assist in management of childhood cancers.
PMID:42727690 | DOI:10.1016/j.jmoldx.2026.08.002
No Free Checker: A Survey of Verifiers for Robot Policies
Hierarchical and Permutation-Invariant Feature Transformation Learning via Policy-Guided Embedding Search
Synergistic Vision-Language Reinforcement Enables Scalable On-Demand Analysis across Diverse Clinical Tasks
City Editing: Hierarchical Agentic Execution for Dependency-Aware Urban Geospatial Modification
Reconstituting human primitive streak formation through extra-embryonic cell coordination
A Non-Canonical Role of SMAD4 in Regulating 3D Genome Architecture to Inhibit Lung Squamous Cell Carcinoma Development
Adv Sci (Weinh). 2026 May 26:e75839. doi: 10.1002/advs.75839. Online ahead of print.
ABSTRACT
Lung squamous cell carcinoma (LUSC) lacks clearly defined key drivers and effective targeted therapies, reflecting an incomplete understanding of its molecular pathogenesis. Here, we identify SMAD4 as a critical regulator of three-dimensional (3D) genome organization in LUSC and uncover a mechanistic link between tumor suppressor loss and oncogenic transcriptional activation. By integrating clinical datasets, genetically engineered mouse models, human and murine LUSC cell lines, and multi-omics analyses, we demonstrate that SMAD4 deficiency promotes LUSC progression by unleashing EP300-mediated enhancer-promoter looping at the SOX2 locus. Mechanistically, SMAD4 does not directly bind SOX2 regulatory elements but instead constrains chromatin looping by sequestering EP300 away from loop anchor regions. Loss of SMAD4 leads to enhanced H3K27ac deposition, aberrant SOX2 activation, and increased LUSC tumor cell proliferation. Together, these findings reveal a non-canonical role for a transcription factor (e.g., SMAD4) in regulating dysregulated 3D genome architecture to inhibit tumor development.
PMID:42189071 | DOI:10.1002/advs.75839
A Non-Canonical Role of SMAD4 in Regulating 3D Genome Architecture to Inhibit Lung Squamous Cell Carcinoma Development
Adv Sci (Weinh). 2026 May 26:e75839. doi: 10.1002/advs.75839. Online ahead of print.
ABSTRACT
Lung squamous cell carcinoma (LUSC) lacks clearly defined key drivers and effective targeted therapies, reflecting an incomplete understanding of its molecular pathogenesis. Here, we identify SMAD4 as a critical regulator of three-dimensional (3D) genome organization in LUSC and uncover a mechanistic link between tumor suppressor loss and oncogenic transcriptional activation. By integrating clinical datasets, genetically engineered mouse models, human and murine LUSC cell lines, and multi-omics analyses, we demonstrate that SMAD4 deficiency promotes LUSC progression by unleashing EP300-mediated enhancer-promoter looping at the SOX2 locus. Mechanistically, SMAD4 does not directly bind SOX2 regulatory elements but instead constrains chromatin looping by sequestering EP300 away from loop anchor regions. Loss of SMAD4 leads to enhanced H3K27ac deposition, aberrant SOX2 activation, and increased LUSC tumor cell proliferation. Together, these findings reveal a non-canonical role for a transcription factor (e.g., SMAD4) in regulating dysregulated 3D genome architecture to inhibit tumor development.
PMID:42189071 | DOI:10.1002/advs.75839
DRIVE: Modeling Skills at the Reasoning and Interaction Levels for Web Agents under Continual Learning
GlobalDentBench: A Multinational Benchmark for Evaluating LLM Clinical Reasoning in Dentistry with Expert Calibration
Towards Multi-Turn Dialog Systems for Industrial Asset Operations and Maintenance
FrontierOR: Benchmarking LLMs' Capacity for Efficient Algorithm Design in Large-Scale Optimization
AutoResearchClaw: Self-Reinforcing Autonomous Research with Human-AI Collaboration
Ferroptosis and macrophage polarization: mechanisms, interplay, and implications for medical applications
Cell Death Discovery, Published online: 23 May 2026; doi:10.1038/s41420-026-03147-2
Ferroptosis and macrophage polarization: mechanisms, interplay, and implications for medical applicationsPRXL2B facilitates the progression of hepatocellular carcinoma and the therapeutic efficacy of oncolytic adenovirus H101 through the PI3K/AKT/PD-L1 axis
Biosci Trends. 2026 May 21. doi: 10.5582/bst.2026.01000. Online ahead of print.
ABSTRACT
Oncolytic adenovirus H101 has shown antitumor activity in hepatocellular carcinoma (HCC), but the molecular determinants of treatment response remain unclear. In this study, a Hepa1-6 subcutaneous tumor model was established in C57BL/6 mice and treated with intratumoral H101, followed by integrated transcriptomic and proteomic analyses to identify candidate genes associated with H101 response. PRXL2B was selected for further investigation using public multi-omics datasets, tissue microarray-based immunohistochemistry, in vitro functional assays, mechanistic analyses, and in vivo validation experiments. Integrated multi-omics analyses identified PRXL2B as a candidate gene downregulated after H101 treatment. Public datasets and tissue-based validation further showed that PRXL2B was upregulated in HCC tissues. In MHCC97H and HCCLM3 cells, PRXL2B knockdown inhibited proliferation, migration, and invasion, promoted apoptosis and cell-cycle arrest, and enhanced the antitumor effect of H101. Mechanistically, PRXL2B silencing reduced AKT phosphorylation and PD-L1 expression. In vivo, PRXL2B knockdown suppressed tumor growth, and the combination of PRXL2B knockdown and H101 produced the strongest antitumor effect. These findings indicate that PRXL2B promotes malignant phenotypes in HCC and may modulate H101 efficacy through the PI3K/AKT/PD-L1 axis. Targeting PRXL2B may therefore represent a potential strategy to enhance the therapeutic efficacy of oncolytic virus therapy in HCC.
PMID:42161529 | DOI:10.5582/bst.2026.01000
A pathogen lncRNA secreted into rice sequesters a host miRNA for virulence
Nature, Published online: 20 May 2026; doi:10.1038/s41586-026-10572-x
A fungal long non-coding RNA from Magnaporthe oryzae translocates into rice cells to sequester a host microRNA that normally represses PKR1, a negative immunity regulator, thereby facilitating infection and revealing a widespread RNA-based pathogen–host interaction mechanism.Pixelated quantum-dot superlattice LEDs
Nature, Published online: 15 April 2026; doi:10.1038/s41586-026-10392-z
Scalable fabrication of ordered perovskite quantum dot superlattices enables high-efficiency, ultrahigh-resolution LEDs and active-matrix displays with greatly improved brightness, stability and device lifetime.